Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise,” and variations such as “comprises” and “comprising,” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.
It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a pharmaceutical carrier” includes mixtures of two or more such carriers, and the like.
Ranges are often expressed herein as from “about” one particular value, and/or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiments.
Phenolic xenobiotics can be modified by cellular systems in a number of ways, e.g., oxidation, glucuronidation, sulphation, methylation, acetylation, etc., and the instability of certain phenolic protein tyrosine kinase (PTK) inhibitors has been documented. For example, the antitumor PTK inhibitor erbstatin, shown below, is known to have a short half-life (<30 min) in fetal calf serum (see, e.g., Umezawa et al., 1991), and the lack of correlation between the activity of tyrphostins, shown below, against isolated enzymes and their effects in vitro and in vivo, is noteworthy (see, e.g., Rambas et al., 1994). Di- and tri-phenolic tyrphostins decompose in solution to more active PTK inhibitors (see, e.g., Faaland et al., 1991), whereas tyrphostins devoid of hydroxy groups have a rapid onset of cellular activity (see, e.g., Reddy et al., 1992), implicating metabolic oxidation to a quinone (or other) moiety as a possible bioactivating step.

Wells et al., 2000, describe several benzothiazole substituted quinol derivatives, shown below, where R1 is —Ac, -Me, -Et, -nPr, or —CH2C≡CH, and R2 is -Me or -Et. These compounds were reported to have activity against certain colon (HCT-116 and HT29) and breast (MCF-7 and MDA468) cancer cell lines in vitro. Note that there is no mention of possible application as thioredoxin/thioredoxin reductase inhibitors.

Stevens et al., 2003, describe various 4-aryl quinols and analogs thereof, including 4-(1H-indol-2-yl)quinols (see page 20 therein), wherein the 1H-indol-2-yl group bears an optional N-substituent (i.e., 1-substituent), denoted RN, which is —H. C1-7alkyl, C3-20heterocyclyl, or C5-20aryl (see page 22 therein). Nowhere in this document is there any teaching or suggestion of a 1-sulfonyl substituent on the 1H-indol-2-yl group (e.g., as RN).

Two compounds that contain a hydroxycyclohexadienone structure and which apparently have antitumor activity have been reported: a hydroxylated flavone-substituted quinol (i.e., a chromone substituted quinol) (see, e.g., Wada et al., 1987) and an oxidized estrone (see, e.g., Milic et al., 1999).

Several related antitumor epoxyquinols, such as Manumycin A (see, e.g., Alcaraz et al., 1998) and LL-C 10037α (see, e.g., Wipf et al., 1994) are known.
